Integrated apparatus for hematological analysis and related method

ABSTRACT

Integrated apparatus and method for hematological analyses, wherein the apparatus comprises, arranged substantially in line and integrated substantially in a single machine, a device ( 14 ) of the optical type to detect substantially instantaneously the speed of blood sedimentation (ESR) by measuring the optical density, or absorbance, of the blood sample, and a measuring assembly ( 18 ) with a cell-counter function or suchlike.

FIELD OF THE INVENTION

The present invention concerns an integrated apparatus to performhematological analyses on blood samples. To be more exact, the inventionconcerns an apparatus that integrates in the same machine at least acell-counter function, or other type of analysis connected with acell-counter function, and the function of detecting the speed of bloodsedimentation, or ESR.

The invention also concerns the method performed by such apparatus.

BACKGROUND OF THE INVENTION

In the field of medical analyses, pathological states, defined asinflammatory, are ascertained by measuring also the speed ofsedimentation of the corpuscular part of the blood (ESR).

Known methods to measure ESR are generally characterized by longanalysis times (from 30 to 60 minutes), which prevent such analysisbeing performed in succession with other, faster analyses, for examplecell-counter analyses.

Moreover, known methods generally have to use throw-away containers,which entails an increase in costs both for purchasing them and fortheir disposal. Furthermore, a great quantity of blood is needed toperform the analysis, normally from 1 to 3 ml, and this entails problemsin particular cases, for example when the analysis is to be made onchildren.

A method to detect the ESR is known, proposed by the same Applicant inEP-A-1.098.188, which provides to take a sample of blood to be analyzed,not diluted and to which no anti-coagulants or other substances havebeen added, from a container in which it is preserved, and to introducethis sample into a capillary tube, which is used for variousmeasurements made on different samples.

This method is based on detecting the optical density or absorbance ofthe blood at a point of the measurement volume, by instantaneouslystopping the flow of blood inside the capillary, in which a photometricsignal correlated to the ESR examination is detected, according to thereference method known as Westergren (see for example the article“Determination of the Length of Sedimentation Reaction . .” by Piva E.,Fassina P. and Plebani M., published in Clin. Chem. Lab. Med. 2002;40(7); pages 713-717)

The study of absorbance over time allows to work out the ERS value byeliminating the initial dead times, and thus considerably reducing theoverall times needed, and obviating the need to use throw-awaycontainers for the analysis. Moreover, the necessary quantity of bloodto be analyzed is smaller and hence the analysis can be carried outwithout difficulty even on pediatric patients.

Another known method for determining the speed of sedimentation of bloodis described in EP-A-0.732.576, also in the name of the presentApplicant. Here too, the method uses the detection of the opticaldensity, or absorbance, of a blood sample at a point of the measurementvolume while said sample is subjected to centrifugal rotation inside acapillary tube.

The study of the absorbance in the blood sample subjected to analysisallows to find other parameters too, correlated to the speed ofsedimentation, such as viscosity, elasticity or density, as indicatedparticularly in EP'188.

Moreover, the characteristics and peculiarities of the analysis made inthis way, particularly the use of a blood sample in movement inside atube, the non-use of throw-away containers and the extremely rapidresponse times, have led the present Applicant to hypothesize that itcan be integrated, in line and with sequential measurements, with othertypes of hematological analyses, such as for example the analysis madeby cell-counters.

Cell-counters are a category of measuring instruments used in clinicalanalysis laboratories which provide the fundamental parameters ofhematology, such as counting red corpuscles, white corpuscles,platelets, hematocrit, and other parameters concerning the form and sizeof the corpuscle part of the blood. In order to perform this analysis,the machine uses a so-called primary blood sample, taken from thepatient and collected in a sealed container which has a top that can beperforated by a needle in order to pick up the sample to be analyzed.

It must be considered that, in diagnostic techniques, the analysisperformed by the cell-counters has always been considered not compatibletime-wise with what is connected to measuring ESR, and hence also withreference to the parameters of viscosity, elasticity, density orsimilar, which can be obtained from the study of absorbance as proposedin EP'188 and EP'576.

In fact, in the state of the art, and before the method to measure ESRas described in EP'188 was developed, the producers of cell-countmachines had never thought of integrating such machines and the devicesused to measure the speed of blood sedimentation into a singleapparatus, because of the intrinsic obstacles and incompatibilities aspointed out above.

It should also be noted that the usual and traditional techniques formeasuring ESR use diluted blood, mixed with anti-coagulants which arenot compatible with subsequent analyses such as those concerning thecell-count, whereas the technique described in EP'188 uses a dry stateanti-coagulant (EDTA) which is the same as that used in primary testtubes used for cell-count analyses.

Document WO-A-95/14224 describes an apparatus that uses the measurementobtained by a cell-counter in order to find, empirically and by means ofcalculations, the ESR value. To be more exact, the apparatus provides afirst analysis section wherein a blood sample is sent to a measuringcell provided with four electrodes, inside which the electric impedanceof the blood sample is measured.

In a second analysis section another blood sample is subjected, possiblyafter being suitably mixed with a diluting product, to a step todetermine the hematocrit. It is necessary to use another blood sample inan apparatus of this type since the measurement of the impedance,performed in the first analysis section, alters the sample irreversibly,which cannot therefore be used in sequence and in line to perform themeasurement of the hematocrit too.

The data relating to the impedance of the blood and its hematocrit, plusthe value of the temperature relating to the impedance measuring cell asmeasured by a suitable measuring element, are sent to a processing unitthat calculates empirically, from these data, the ESR value.

The limits and disadvantages of an apparatus of this type are first ofall its complexity and the large number of components it requires, bothto detect the parameters and also to calculate and process the data.

Above all, however, the result obtained does not guarantee reliabilityand precision, on the one hand because intrinsically the empiricalcalculation process does not allow to ensure that precise values areobtained, and on the other hand because it adds together errors oftolerance due to no fewer than three different measuring systems.

It must in any case be considered that, in substance, this knownapparatus does not perform an analytical and reliable measurement, inline, in sequence, and with the same blood sample, both of the speed ofblood sedimentation and also of the hematocrit.

The purpose of the invention is therefore to achieve a device andpropose a relative method to perform hematological analyses whichintegrates, in a single apparatus—small, compact and easy totransport—the functions of measuring, in line, in close sequence andwith the same blood sample, the speed of blood sedimentation (ESR) in amachine able to perform at least the cell-count function and/or otherconnected analyses.

The Applicant has devised and embodied the present invention in order toobtain this purpose and other advantages as shown hereafter.

SUMMARY OF THE INVENTION

The present invention is set forth and characterized in the respectivemain claims, while the dependent claims describe other characteristicsof the present invention.

The integrated apparatus according to the present invention comprises atleast a collection element for one or more suitably sealed containers;each container is equipped with a relative top suitable to be perforatedby means of at least a pick-up needle, in order to pick up the sample tobe analyzed, in a quantity of between 30 and 200 μl.

The sealed container is a so-called “primary test tube” normally used incell-count machines, wherein the blood remains in a state of rest, andonly a dry state anti-coagulant of the EDTA type is added, and it is notfurther diluted or mixed with other liquid or solid substances.

This sample is sent, by means of pump means and through a circulationcircuit, inside a capillary tube cooperating with an optical systemsuitable to emit electromagnetic radiations in the field of 100-1500 nm,advantageously 200-1000 nm, and to detect the radiation transmittedthrough the sample after having interrupted the flow of bloodinstantaneously, according to the teaching of EP'188. From thistransmitted radiation, the ESR value is obtained by studying the opticaldensity, or absorbance, of the blood sample as described for example inEP'576.

Since this analysis is performed in line, since it is not destructiveand does not change in any way the initial chemical-physicalcharacteristics of the blood sample—quite the contrary, for example, ofa measurement of impedance—the same sample can then be sent,substantially without any break in continuity, and in a very closesequence, inside the measuring assembly of the cell-counter in order toperform the processes connected with such measurement.

After the measurements made by the cell-counter, the blood sample isdischarged into a discharge container.

According to a variant, at least some of the measuring components of thecell-counters are located upstream of the device to measure the ESR.

With this system, therefore, the same device, of the type with a pick-upneedle, and the same system with a pump that feeds the blood sample, canbe shared both by the device that measures the ESR and also by the onethat functions as a cell-counter.

The two measuring devices can therefore be arranged in series together,at a close distance from each other, and the whole thing can be housedinside a small container, compact, transportable and easily locatedinside a laboratory or a hospital surgery.

According to a variant, a single pick-up needle is connected to twopaths that divide, one passing through the optical system to measure theESR and the other through the cell-counter measuring systems orsuchlike.

According to another, although less advantageous variant, two pick-upneedles are used to pick up the respective samples to be sent to therelative measuring systems.

The two measuring systems are commanded and governed by the same commandand control unit which selectively activates and coordinates thefunctioning thereof; the command and control unit is associated in knownmanner with interfaces that connect and communicate with the outside,such as a monitor, a keyboard to forward commands and to insert data andparameters, and possibly a printer to print out the values resultingfrom the analyses. According to a variant, the measuring system isconnected on line for the automatic exchange of information betweenremote users.

In one embodiment of the invention, the pump means are reversible andallow to invert the flow inside the circuit; it is thus possible tore-homogenize the blood sample and rapidly repeat measurements thereon.

The capillary is also able to be thermostated in order to allow analysisto be carried out at a constant temperature, which can be pre-set asdesired.

BRIEF DESCRIPTION OF THE DRAWING

These and other characteristics of the present invention will becomeclear from the following description of a preferential form ofembodiment, given as a non-restrictive example, with reference to FIG. 1, which is a schematic view of an integrated apparatus for hematologicalanalyses according to the invention.

DETAILED DESCRIPTION OF A PREFERENTIAL EMBODIMENT

FIG. 1 shows a schematic view of an apparatus 10 which integrates thefunction of determining the speed of sedimentation of blood and otherparameters connected thereto, with the function of cell-counter, orother connected measurement.

The apparatus 10 comprises as its main components:

-   -   a pick-up member 11, of the needle type, able to selectively        pick up a sample of blood to be analyzed from containers 22        housed in a storage drum 23, which can be made to rotate by a        motor 21 in order to mix the blood;    -   a device to measure the ESR 14 comprising a capillary container        12, transparent to electromagnetic radiations in a field between        100 and 1500 nm, preferentially between 200and 1000 nm, inside        which the blood sample is able to be introduced;    -   a circuit 13 which connects the pick-up member 11 to the        capillary 12 and inside which the blood sample is able to        circulate;    -   an instant block pump 28 associated with the circuit 13;    -   an optical system associated with the capillary 12 and        comprising at least a device 16 to emit electromagnetic        radiations associated with a mating detector device 17, arranged        on opposite sides with respect to a point of the capillary 12;    -   a measuring assembly 18, arranged in series with the capillary        12 and inside which the blood sample, after the speed of        sedimentation has been measured, is able to circulate so that        hematological measurements can be performed, such as counting        the red cells, white cells, platelets, the hematocrit and other        parameters relating to the form and size of the corpuscle part        of the blood;    -   a discharge tank 19, where the blood sample which has been        subjected to analysis is discharged and then disposed of;    -   a command and control unit 20 able to manage the functioning of        the apparatus 10 and    -   a plurality of interfaces, such as a monitor 24, keyboard 25 and        printer 26, connected to the control unit 20 in order to set the        functions of the apparatus 10, to display and print the results        and possibly to connect on line in order to transmit and        exchange information.

The command and control unit 20, by means of electric cables 27, governsand controls the functioning of the pick-up member 11, the stirrer motor21, the block pump 28, a the optical system 16, 17 in order to determinethe ESR, and the measuring assembly 18.

With the apparatus 10 as described above, a blood sample can be pickedup, by means of the needle member 11, from one of the containers 22arranged in the storage drum 23. The blood sample is sent, through thecircuit 13 and the pump 28, inside the capillary 12 where, by means ofthe pump, it is instantaneously stopped in order to measure the ESR withthe slopped-flow process described in EP'188.

Then, the flow is re-started by making the same blood sample (which hasnot undergone any chemical-physical alteration during the measurement ofthe ESR) pass without any break in continuity through the cell-countermeasuring assembly 18, which performs the desired measurements, and fromwhich the blood sample is then discharged into the tank 19.

In this way, the times to perform the desired measurements are reducedto a minimum, the quantity of blood to be used, and hence to be takenfrom the patient, can be greatly reduced, in the range of 30-200 μl,without needing to be diluted or have other reagents or anti-coagulantsadded. Moreover, the procedures to transfer the samples from one machineto the other are eliminated and hence the whole analysis is easier,quicker and more rational, also reducing the risks that additionalhandling might lead to exchanges and mistakes in identifying the sample.

The pump that makes the blood sample circulate in the circuit 13 can bearranged either upstream or downstream of the capillary 12 and, in apreferential embodiment, is of the reversible type and allows the bloodto circulate in both directions.

According to a variant that is not shown here, the circulation circuit13 is divided into two branches, a first passing through the device 14to measure the ESR, and a second passing through the measuring assembly18 which counts the cells.

The data acquired by the measuring devices 14 and 18 are transmitted inreal time to the command and control unit 20 which memorizes them andprocesses them in order to obtain the ESR value, and correlatedparameters, and also the count of the cells and the other valuesobtained in the measuring assembly 18. The data acquired can be comparedor integrated with parameters present in a database inside the unit 20.

The results of the analysis can then be displayed on the display 24and/or printed by the printer 26 while the blood sample is dischargedinto the tank 19. By obtaining the ESR values and, for example, thehematocrit simultaneously and with the same equipment, the analyst alsohas the advantage that he can make the desired comparisons andcorrections according to the crossed parametric comparison of therespective values.

It is clear, however, that modifications and/or additions can be made tothe apparatus 10 and method as described heretofore, without departingfrom the field and scope of the present invention.

For example, as we said, some components of the measuring assembly 18can be upstream of the device 14 to detect the ESR. The instantaneousblockage of the flow of the blood sample along the circuit 13 can beperformed by means of valve means associated with the circuit 13 and/orthe capillary container 12.

1. Integrated apparatus for hematological analyses, wherein itcomprises, arranged substantially in line and integrated substantiallyin a single machine, an optical device to detect substantiallyinstantaneously the speed of blood sedimentation (ESR) by measuring theoptical density, or absorbance, of a blood sample, and a measuringassembly with a cell-counter function, said optical device for thedetection of the ESR and said measuring assembly sharing a circuit forcirculation of the same blood sample to be subjected first to thedetection of the ESR and then to other measurements such as counting thered cells, white cells, platelets, the hematocrit and other parametersrelating to the form and size of the corpuscle part of the blood, saidoptical device for the detection of the ESR and said measuring assemblywith a cell-counter function sharing a pump associated on the circuitand for circulating the blood sample, said apparatus further including asingle command and control unit controlling and governing thefunctioning of said optical device to detect the speed of bloodsedimentation and said measuring assembly.
 2. Integrated apparatus as inclaim 1, wherein said optical device to detect the speed of bloodsedimentation is arranged in series with said measuring assembly. 3.Integrated apparatus as in claim 1, further comprising a blood samplesource, the blood sample source is common to both said optical devicefor the detection of the ESR and said measuring assembly with acell-counter function, wherein said optical device for the detection ofthe ESR and said measuring assembly with a cell-counter function areboth disposed downstream of the blood sample source.
 4. Integratedapparatus as in claim 1, further comprising a collection element for oneor more containers containing blood samples, associated with a pick-upmember, said pick-up member being in fluid communication with saidoptical device so as to be able to make a sample of said blood circulatein close sequence and substantially without any break in continuitythrough a capillary tube of said optical device to detect the ESR andthrough said measuring assembly with cell-counter function. 5.Integrated apparatus as in claim 4, wherein said pick-up member includesa needle member, said one or more containers having a sealing top ableto be perforated by said needle member.
 6. Integrated apparatus as inclaim 4, wherein said optical device includes means for instantaneouslyinterrupting the blood flow (stopped flow) along said capillary tube. 7.Method to perform hematological analyses, wherein it provides that ablood sample, taken under control of a single command and control unitfrom a container by means of a pick-up needle member, is sent to andmade to circulate in a single circuit which passes in close sequence,and substantially without any break in continuity, first through anoptical device under control of the single command and control unit todetect substantially instantaneously the speed of blood sedimentation(ESR) by measuring the optical density, or absorbance, of the bloodsample, and then through a measuring assembly under control of thesingle command and control unit to count the cells, or other measurementconnected with counting cells, wherein said optical device and saidmeasuring assembly are a single machine sharing a pump associated on thesingle circuit, and are arranged in line and without any break incontinuity in order to be able to perform on the same blood sample firstthe measurement of the ESR and then other measurements such as countingthe red cells, white cells, platelets, the hematocrit and otherparameters relating to the form and size of the corpuscle part of theblood.
 8. Method as in claim 7, wherein the speed of blood sedimentationis detected by means of an instantaneous stoppage of the flow of theblood sample passing in a capillary tube of said optical device, and bysending an optic beam through said capillary tube in order to detect theoptical density at the point of stoppage of the blood inside thecapillary tube, after which detection of the flow of blood is restartedfor transit through said measuring assembly.